Tachypnea and Antipyresis in Febrile Horses after Sedation with α2-Agonists

Kendall, Anna; Mosley, Craig; Bröjer, Johan

doi:10.1111/j.1939-1676.2010.0528.x

Cited by 17 publications

(7 citation statements)

References 14 publications

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“…The reason for this unexpected increase in RR is not known. Tachypnea following the administration of xylazine and detomidine has been described in febrile horses (Kendall et al ., ), but horses in this study had normal rectal temperatures. Another possibility could be the development of hypoxemia associated with drug‐related changes in gas exchange, compounded further by altitude (study performed at a barometric pressure of 635 mmHg).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of intravenous dexmedetomidine in the horse

Rezende

Grimsrud

Stanley

et al. 2014

Vet Pharm & Therapeutics

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The aim of the study was to describe the pharmacokinetics and selected pharmacodynamics of intravenous dexmedetomidine in horses. Eight adult horses received 5 μg/kg dexmedetomidine IV. Blood samples were collected before and for 10 h after drug administration to determine dexmedetomidine plasma concentrations. Pharmacokinetic parameters were calculated using noncompartmental analysis. Data from one outlier were excluded from the statistical summary. Behavioral and physiological responses were recorded before and for 6 h after dexmedetomidine administration. Dexmedetomidine concentrations decreased rapidly (elimination half-life of 8.03 ± 0.84 min). Time of last detection varied from 30 to 60 min. Bradycardia was noted at 4 and 10 min after drug administration (26 ± 8 and 29 ± 8 beats/min respectively). Head height decreased by 70% at 4 and 10 min and gradually returned to baseline. Ability to ambulate was decreased for 60 min following drug administration, and mechanical nociceptive threshold was increased during 30 min. Blood glucose peaked at 30 min (134 ± 24 mg/dL) and borborygmi were decreased for the first hour after dexmedetomidine administration. Dexmedetomidine was quickly eliminated as indicated by the rapid decrease in plasma concentrations. Physiological, behavioral, and analgesic effects observed after dexmedetomidine administration were of short duration.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of intravenous dexmedetomidine in the horse

Rezende

Grimsrud

Stanley

et al. 2014

Vet Pharm & Therapeutics

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“…Alpha-2 AR agonists cause a modest hypothermia in the rodent (Millan et al, 2000; Lahdesmaki et al, 2003), attenuate febrile responses in rabbits (Szreder, 1997) and horses (Kendall et al, 2010) and reduce human shivering in clinical hypothermic settings (Weant et al, 2010; Logan et al, 2011). Early studies to identify the site and mechanism underlying the hypothermic effects of α2-AR agonists focused on the thermoregulatory circuits in the preoptic area (Mallick and Alam, 1992; Quan et al, 1992; Romanovsky et al, 1993; Millan et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

α2 Adrenergic Receptor-Mediated Inhibition of Thermogenesis

et al. 2013

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Alpha2-adrenergic receptor (α2-AR) agonists have been use as anti-hypertensive agents, in the management of drug withdrawal, and as sedative analgesics. Since α2-AR agonists also influence the regulation of body temperature, we explored their potential as antipyretic agents. This study delineates the central neural substrate for the inhibition of rat brown adipose tissue (BAT) and shivering thermogenesis by α2-AR agonists. Nanoinjection of the α2-AR agonist, clonidine (1.2 nmol), into the rostral raphe pallidus (rRPa) inhibited BAT sympathetic nerve activity (SNA) and BAT thermogenesis. Subsequent nanoinjection of the α2-AR antagonist, idazoxan (6nmol) into the rRPa reversed the clonidine-evoked inhibition of BAT SNA and BAT thermogenesis. Systemic administration of the α2-AR agonists, dexmedetomidine (25ug/kg, iv) or clonidine (100ug/kg, iv) inhibited shivering EMGs, BAT SNA and BAT thermogenesis effects that were reversed by nanoinjection of idazoxan (6nmol) into the rRPa. Dexmedetomidine (100µg/kg, ip) prevented and reversed lipopolysaccharide (10µg/kg ip)-evoked thermogenesis in free-behaving rats. Cholera toxin subunit b retrograde tracing from rRPa and pseudorabies virus transynaptic retrograde tracing from BAT combined with immunohistochemistry for catecholaminergic biosynthetic enzymes revealed the ventrolateral medulla as the source of catecholaminergic input to the rRPa and demonstrated that these catecholaminergic neurons are synaptically connected to BAT. Photostimulation of VLM neurons expressing of the PRSx8-ChR2-mCherry lentiviral vector inhibited BAT SNA via activation of α2-ARs in the rRPa. These results indicate a potent inhibition of BAT and shivering thermogenesis by α2-AR activation in the rRPa, and suggest a therapeutic potential of α2-AR agonists for reducing potentially-lethal elevations in body temperature during excessive fever.

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“…NE injected into the PVH caused a biphasic response (inhibition followed by excitation) in BAT SNA (316). In addition, systemic administration of an α2 adrenergic receptor agonist causes a modest hypothermia (170,214) and prevents febrile responses (158,199,368) likely via activation of α2 adrenergic receptors on sympathetic premotor neurons for BAT in the rRPa (126), which inhibits BAT SNA and BAT thermogenesis (199). Cat-echolamine inputs to the POA, the PVH and the rRPa arise from neurons in the C1 and A1 cell groups in the VLM (78, 199, 325, 385).…”

Section: Neurochemical Modulation Of Bat Thermogenesismentioning

confidence: 99%

Central Nervous System Regulation of Brown Adipose Tissue

Morrison

Madden

2014

Comprehensive Physiology

120

103

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Thermogenesis, the production of heat energy, in brown adipose tissue is a significant component of the homeostatic repertoire to maintain body temperature during the challenge of low environmental temperature in many species from mouse to man and plays a key role in elevating body temperature during the febrile response to infection. The sympathetic neural outflow determining brown adipose tissue (BAT) thermogenesis is regulated by neural networks in the CNS which increase BAT sympathetic nerve activity in response to cutaneous and deep body thermoreceptor signals. Many behavioral states, including wakefulness, immunologic responses, and stress, are characterized by elevations in core body temperature to which central command-driven BAT activation makes a significant contribution. Since energy consumption during BAT thermogenesis involves oxidation of lipid and glucose fuel molecules, the CNS network driving cold-defensive and behavioral state-related BAT activation is strongly influenced by signals reflecting the short and long-term availability of the fuel molecules essential for BAT metabolism and, in turn, the regulation of BAT thermogenesis in response to metabolic signals can contribute to energy balance, regulation of body adipose stores and glucose utilization. This review summarizes our understanding of the functional organization and neurochemical influences within the CNS networks that modulate the level of BAT sympathetic nerve activity to produce the thermoregulatory and metabolic alterations in BAT thermogenesis and BAT energy expenditure that contribute to overall energy homeostasis and the autonomic support of behavior.

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Tachypnea and Antipyresis in Febrile Horses after Sedation with α2-Agonists

Cited by 17 publications

References 14 publications

Pharmacokinetics and pharmacodynamics of intravenous dexmedetomidine in the horse

Pharmacokinetics and pharmacodynamics of intravenous dexmedetomidine in the horse

α2 Adrenergic Receptor-Mediated Inhibition of Thermogenesis

Central Nervous System Regulation of Brown Adipose Tissue

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